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Snaclecs (Snake C-Type Lectins) that Activate Platelets

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Toxins and Hemostasis

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Abstract

One of the major targets for snake venom proteins is haemostasis. This weakens the prey and helps with swallowing and digestion. The venom proteins act either on coagulation factor or on platelets. Snake venom proteins mainly adapt physiological mechanisms to inhibit or activate platelets. The most efficient way for snake venom to reduce platelet function is not by inhibiting the function of individual or several receptors but rather by activating platelets so that they are removed from the circulation producing thrombocytopenia. Platelets can be activated efficiently by an agonist using low molecule numbers in two main ways already used physiologically. One of these is by proteases acting on proteolytically activated receptors. The other major route is by clustering receptors mimicking physiological ligands such as von Willebrand factor and collagen. The snaclecs described in this chapter fall into this latter category. Their targets are those of the physiological ligands and include GPIb, GPVI, α2β1 and the recently discovered CLEC2.

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References

  • Batuwangala, T., Leduc, M., Gibbins, J.M., Bon, C., Jones, E.Y., 2004. Structure of the snake-venom toxin convulxin. Acta Crystallogr. D. Biol. Crystallogr. 60, 46–53.

    Article  PubMed  Google Scholar 

  • Bergmeier, W., Bouvard, D., Eble, J.A., Mokhtari-Nejad, R., Schulte, V., Zirngibl, H., Brakebusch, C., Fassler, R., Nieswandt, B., 2001. Rhodocytin (aggretin) activates platelets lacking α2β1 integrin, GPVI, and the ligand binding domain of GPIbα. J. Biol. Chem. 276, 25121–25126.

    Article  PubMed  CAS  Google Scholar 

  • Brinkhous, K.M., Read, M.S., Fricke, W.A., Wagner, R.H., 1983. Botrocetin (venom coagglutinin): reaction with a broad spectrum of multimeric forms of factor VIII macromolecular complex. Proc. Natl. Acad. Sci. U.S.A. 80, 1463–1466.

    Article  PubMed  CAS  Google Scholar 

  • Chang, C.H., Chung, C.H., Kuo, H.L., Hsu, C.C., Huang, T.F., 2008. The highly specific platelet glycoprotein (GP) VI agonist trowaglerix impaired collagen-induced platelet aggregation ex vivo through matrix metalloproteinase-dependent GPVI shedding. J. Thromb. Haemost. 6, 669–676.

    Article  PubMed  CAS  Google Scholar 

  • Chen, Y.S., Huang, C.H., Chiou, S.H., 2010. Characterization and molecular cloning of one novel C-type lectin from the venom of Taiwan habu (Trimeresurus mucrosquamatus) Toxicon 55, 762–772.

    Article  PubMed  CAS  Google Scholar 

  • Cheng, X., Qian, Y., Liu, Q., Li, B.X., Zhang, M., Liu, J., 1999. Purification, characterization, and cDNA cloning of a new fibrinogenlytic venom protein, Agkisacutacin, from Agkistrodon acutus venom. Biochem. Biophys. Res. Commun. 265, 530–535.

    Article  PubMed  CAS  Google Scholar 

  • Cheng, X., Xu, Z.Y., Liu, Q.D., Li, X.M., Li, X.Y., Liu, J., 2000. Purification and characterization of a platelet agglutinating inhibiting protein (Agkisacutacin) from Agkistrodon acutus venom. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai) 32, 653–656.

    CAS  Google Scholar 

  • Chiou, S.H., Huang, K.F., Chow, L.P., Tsugita, A., Wu, S.H., 1996. Isolation of a venom factor devoid of proteolytic activity from Taiwan habu (Trimeresurus mucrosquamatus): N-terminal sequence homology and no functional similarity to factors IX/X-binding proteins and botrocetin. J. Protein Chem. 15, 667–674.

    Article  PubMed  CAS  Google Scholar 

  • Chung, C.H., Au, L.C., Huang, T.F., 1999. Molecular cloning and sequence analysis of aggretin, a collagen-like platelet aggregation inducer. Biochem. Biophys. Res. Commun. 263, 723–727.

    Article  PubMed  CAS  Google Scholar 

  • Clemetson, K.J., Morita, T., Kini, R.M., 2009. Scientific and standardization committee communications: classification and nomenclature of snake venom C-type lectins and related proteins. J. Thromb. Haemost. 7, 360.

    Article  PubMed  CAS  Google Scholar 

  • Dormann, D., Clemetson, J.M., Navdaev, A., Kehrel, B.E., Clemetson, K.J., 2001. Alboaggregin A activates platelets by a mechanism involving glycoprotein VI as well as glycoprotein Ib. Blood 97, 929–936.

    Article  PubMed  CAS  Google Scholar 

  • Du, X.Y., Clemetson, J.M., Navdaev, A., Magnenat, E.M., Wells, T N., Clemetson, K.J., 2002a. Ophioluxin, a convulxin-like C-type lectin from Ophiophagus hannah (King cobra) is a powerful platelet activator via glycoprotein VI. J. Biol. Chem. 277, 35124–35132.

    Article  PubMed  CAS  Google Scholar 

  • Du, X.Y., Magnenat, E., Wells, T.N., Clemetson, K.J., 2002b. Alboluxin, a snake C-type lectin from Trimeresurus albolabris venom is a potent platelet agonist acting via GPIb and GPVI. Thromb. Haemost. 87, 692–698.

    CAS  Google Scholar 

  • Du, X.Y., Navdaev, A., Clemetson, J.M., Magnenat, E., Wells, T.N., Clemetson, K.J., 2001. Bilinexin, a snake C-type lectin from Agkistrodon bilineatus venom agglutinates platelets via GPIb and α2β1. Thromb. Haemost. 86, 1277–1283.

    PubMed  CAS  Google Scholar 

  • Flood, V.H., Friedman, K.D., Gill, J.C., Morateck, P.A., Wren, J.S., Scott, J.P., Montgomery, R.R., 2009. Limitations of the ristocetin cofactor assay in measurement of von Willebrand factor function. J. Thromb. Haemost. 7, 1832–1839.

    Article  PubMed  CAS  Google Scholar 

  • Fry, B.G., Vidal, N., Norman, J.A., Vonk, F.J., Scheib, H., Ramjan, S.F., Kuruppu, S., Fung, K., Hedges, S.B., Richardson, M.K., Hodgson, W.C., Ignjatovic, V., Summerhayes, R., Kochva, E., 2006. Early evolution of the venom system in lizards and snakes. Nature 439, 584–588.

    Article  PubMed  CAS  Google Scholar 

  • Fukuda, K., Doggett, T., Laurenzi, I.J., Liddington, R.C., Diacovo, T.G. 2005. The snake venom protein botrocetin acts as a biological brace to promote dysfunctional platelet aggregation. Nat. Struct. Mol. Biol. 12, 152–159.

    Article  PubMed  CAS  Google Scholar 

  • Fukuda, K., Doggett, T.A., Bankston, L.A., Cruz, M.A., Diacovo, T.G., Liddington, R.C., 2002. Structural basis of von Willebrand factor activation by the snake toxin botrocetin. Structure 10, 943–950.

    Article  PubMed  CAS  Google Scholar 

  • Fukuda, K., Mizuno, H., Atoda, H., Morita, T., 2000. Crystal structure of flavocetin-A, a platelet glycoprotein Ib-binding protein, reveals a novel cyclic tetramer of C-type lectin-like heterodimers. Biochemistry 39, 1915–1923.

    Article  PubMed  CAS  Google Scholar 

  • Hamako, J., Matsui, T., Suzuki, M., Ito, M., Makita, K., Fujimura, Y., Ozeki, Y., Titani, K., 1996. Purification and characterization of bitiscetin, a novel von Willebrand factor modulator protein from Bitis arietans snake venom. Biochem. Biophys. Res. Commun. 226, 273–279.

    Article  PubMed  CAS  Google Scholar 

  • Hirotsu, S., Mizuno, H., Fukuda, K., Qi, M.C., Matsui, T., Hamako, J., Morita, T., Titani, K., 2001. Crystal structure of bitiscetin, a von Willebrand factor-dependent platelet aggregation inducer. Biochemistry 40, 13592–13597.

    Article  PubMed  CAS  Google Scholar 

  • Hooley, E., Papagrigoriou, E., Navdaev, A., Pandey, A.V., Clemetson, J.M., Clemetson, K.J., Emsley, J., 2008. The crystal structure of the platelet activator aggretin reveals a novel (αβ)2 dimeric structure. Biochemistry 47, 7831–7837.

    Article  PubMed  CAS  Google Scholar 

  • Horii, K., Brooks, M.T., Herr, A.B., 2009. Convulxin forms a dimer in solution and can bind eight copies of glycoprotein VI: implications for platelet activation. Biochemistry 48, 2907–2914.

    Article  PubMed  CAS  Google Scholar 

  • Howard, M.A. and Firkin, B.G., 1971. Ristocetin – a new tool in the investigation of platelet aggregation. Thromb. Diath. Haemorrh. 26, 362–369.

    PubMed  CAS  Google Scholar 

  • Huang, K.F., Ko, T.P., Hung, C.C., Chu, J., Wang, A.H., Chiou, S.H., 2004. Crystal structure of a platelet-agglutinating factor isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus). Biochem. J. 378, 399–407.

    Article  PubMed  CAS  Google Scholar 

  • Kanaji, S., Kanaji, T., Furihata, K., Kato, K., Ware, J.L., Kunicki, T.J. 2003. Convulxin binds to native, human glycoprotein Ibα (GPIbα). J. Biol. Chem. 278, 39452–39460.

    Article  PubMed  CAS  Google Scholar 

  • Kaneko, M.K., Kato, Y., Kameyama, A., Ito, H., Kuno, A., Hirabayashi, J., Kubota, T., Amano, K., Chiba, Y., Hasegawa, Y., Sasagawa, I., Mishima, K., Narimatsu, H., 2007. Functional glycosylation of human podoplanin: glycan structure of platelet aggregation-inducing factor. FEBS Lett. 581, 331–336.

    Article  PubMed  CAS  Google Scholar 

  • Kato, Y., Kaneko, M.K., Kunita, A., Ito, H., Kameyama, A., Ogasawara, S., Matsuura, N., Hasegawa, Y., Suzuki-Inoue, K., Inoue, O., Ozaki, Y., Narimatsu, H., 2008. Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Cancer Sci. 99, 54–61.

    PubMed  CAS  Google Scholar 

  • Kerrigan, A.M., Dennehy, K.M., Mourão-Sá, D., Faro-Trindade, I., Willment, J.A., Taylor, P.R., Eble, J.A., Reis e Sousa, C., Brown, G.D., 2009. CLEC-2 is a phagocytic activation receptor expressed on murine peripheral blood neutrophils. J. Immunol. 182, 4150–4157.

    Article  PubMed  CAS  Google Scholar 

  • Kowalska, M.A., Tan, L., Holt, J.C., Peng, M., Karczewski, J., Calvete, J.J., Niewiarowski, S., 1998. Alboaggregins A and B. Structure and interaction with human platelets. Thromb. Haemost. 79, 609–613.

    PubMed  CAS  Google Scholar 

  • Kunita, A., Kashima, T.G., Morishita, Y., Fukayama, M., Kato, Y., Tsuruo, T., Fujita, N., 2007. The platelet aggregation-inducing factor aggrus/podoplanin promotes pulmonary metastasis. Am. J. Pathol. 170, 1337–1347.

    Article  PubMed  CAS  Google Scholar 

  • Leduc, M., Bon, C., 1998. Cloning of subunits of convulxin, a collagen-like platelet-aggregating protein from crotalus durissus terrificus venom. Biochem. J. 333, 389–393.

    PubMed  CAS  Google Scholar 

  • Lee, W.H., Du, X.Y., Lu, Q.M., Clemetson, K.J., Zhang, Y., 2003. Stejnulxin, a novel snake C-type lectin-like protein from Trimeresurus stejnegeri venom is a potent platelet agonist acting specifically via GPVI. Thromb. Haemost. 90, 662–671.

    PubMed  CAS  Google Scholar 

  • Li, X., Zheng, L., Kong, C., Kolatkar, P.R., Chung, M.C., 2004. Purpureotin: a novel di-dimeric C-type lectin-like protein from Trimeresurus purpureomaculatus venom is stabilized by noncovalent interactions. Arch. Biochem. Biophys. 424, 53–62.

    Article  PubMed  CAS  Google Scholar 

  • Liu, S., Zhu, Z., Sun, J., Huang, Q., Teng, M., Niu, L., 2002. Purification, crystallization and preliminary X-ray crystallographic analysis of agkaggregin, a C-type lectin-like protein from Agkistrodon acutus venom. Acta Crystallogr. D. Biol. Crystallogr. 58, 675–678.

    Article  PubMed  Google Scholar 

  • Lu, Q., Navdaev, A., Clemetson, J.M., Clemetson, K.J., 2004. GPIb is involved in platelet aggregation induced by mucetin, a snake C-type lectin protein from Chinese habu (Trimeresurus mucrosquamatus) venom. Thromb. Haemost. 91, 1168–1176.

    PubMed  CAS  Google Scholar 

  • Maita, N., Nishio, K., Nishimoto, E., Matsui, T., Shikamoto, Y., Morita, T., Sadler, J.E., Mizuno, H., 2003. Crystal structure of von Willebrand factor A1 domain complexed with snake venom, bitiscetin: insight into glycoprotein Ibα binding mechanism induced by snake venom proteins. J. Biol. Chem. 278, 37777–37781.

    Article  PubMed  CAS  Google Scholar 

  • Mizuno, H., Fujimoto, Z., Atoda, H., Morita, T., 2001. Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X. Proc. Natl. Acad. Sci. U.S.A. 98, 7230–7234.

    Article  PubMed  CAS  Google Scholar 

  • Mizuno, H., Fujimoto, Z., Koizumi, M., Kano, H., Atoda, H., Morita, T., 1999. Crystal structure of coagulation factor IX-binding protein from habu snake venom at 2.6 Å: implication of central loop swapping based on deletion in the linker region. J. Mol. Biol. 289, 103–112.

    Article  PubMed  CAS  Google Scholar 

  • Murakami, M.T., Zela, S.P., Gava, L.M., Michelan-Duarte, S., Cintra, A.C., Arni, R.K., 2003. Crystal structure of the platelet activator convulxin, a disulfide-linked α4β4 cyclic tetramer from the venom of Crotalus durissus terrificus. Biochem. Biophys. Res. Commun. 310, 478–482.

    Article  PubMed  CAS  Google Scholar 

  • Navdaev, A., Clemetson, J.M., Polgar, J., Kehrel, B.E., Glauner, M., Magnenat, E., Wells, T.N., Clemetson, K.J., 2001. Aggretin, a heterodimeric C-type lectin from Calloselasma rhodostoma (Malayan pit viper) stimulates platelets by binding to α2β1 integrin and GPIb, activating Syk and PLCγ2, but does not involve the GPVI/Fcγ collagen receptor. J. Biol. Chem. 276, 20882–20889.

    Article  PubMed  CAS  Google Scholar 

  • Navdaev, A., Dormann, D., Clemetson, J.M., Clemetson, K.J., 2001. Echicetin, a GPIb-binding snake C-type lectin from Echis carinatus, also contains a binding site for IgMκ responsible for platelet agglutination in plasma and inducing signal transduction. Blood 97, 2333–2341.

    Article  PubMed  CAS  Google Scholar 

  • Peng, M., Holt, J.C., Niewiarowski, S., 1994. Isolation, characterization and amino acid sequence of echicetin β-subunit, a specific inhibitor of von Willebrand factor and thrombin interaction with glycoprotein Ib. Biochem. Biophys. Res. Commun. 205, 68–72.

    Article  PubMed  CAS  Google Scholar 

  • Peng, M., Lu, W., Kirby, E.P., 1991. Alboaggregin-B: A new platelet agonist that binds to platelet membrane glycoprotein Ib. Biochemistry 30, 11529–11536.

    Article  PubMed  CAS  Google Scholar 

  • Peng, M., Lu, W., Kirby, E.P., 1992. Characterization of three alboaggregins purified from Trimeresurus albolabris venom. Thromb. Haemost. 67, 702–707.

    PubMed  CAS  Google Scholar 

  • Polgar, J., Clemetson, J.M., Kehrel, B.E., Wiedemann, M., Magnenat, E.M., Wells, T.N.C., Clemetson, K.J., 1997. Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor. J. Biol. Chem. 272, 13576–13583.

    Article  PubMed  CAS  Google Scholar 

  • Polgar, J., Magnenat, E.M., Peitsch, M.C., Wells, T.N., Saqi, M.S., Clemetson, K.J., 1997. Amino acid sequence of the alpha subunit and computer modelling of the alpha and beta subunits of echicetin from the venom of Echis carinatus (saw-scaled viper). Biochem. J. 323, 533–537.

    PubMed  CAS  Google Scholar 

  • Rucavado, A., Soto, M., Kamiguti, A.S., Theakston, R.D., Fox, J.W., Escalante, T., Gutierrez, J.M., 2001. Characterization of aspercetin, a platelet aggregating component from the venom of the snake Bothrops asper which induces thrombocytopenia and potentiates metalloproteinase-induced hemorrhage. Thromb. Haemost. 85, 710–715.

    PubMed  CAS  Google Scholar 

  • Sakurai, Y., Fujimura, Y., Kokubo, T., Imamura, K., Kawasaki, T., Handa, M., Suzuki, M., Matsui, T., Titani, K., Yoshioka, A., 1998. The cDNA cloning and molecular characterization of a snake venom platelet glycoprotein Ib-binding protein, mamushigin, from Agkistrodon halys blomhoffii venom. Thromb. Haemost. 79, 1199–1207.

    PubMed  CAS  Google Scholar 

  • Sen, U., Vasudevan, S., Subbarao, G., McClintock, R.A., Celikel, R., Ruggeri, Z.M., Varughese, K.I., 2001. Crystal structure of the von Willebrand factor modulator botrocetin. Biochemistry 40, 345–352.

    Article  PubMed  CAS  Google Scholar 

  • Shin, Y., Okuyama, I., Hasegawa, J., Morita, T., 2000. Molecular cloning of glycoprotein Ib-binding protein, flavocetin-A, which inhibits platelet aggregation. Thromb. Res. 99, 239–247.

    Article  PubMed  CAS  Google Scholar 

  • Suzuki-Inoue, K., Fuller, G.L., García, A., Eble, J.A., Pöhlmann, S., Inoue, O., Gartner, T.K., Hughan, S.C., Pearce, A.C., Laing, G.D., Theakston, R.D., Schweighoffer, E., Zitzmann, N., Morita, T., Tybulewicz, V.L., Ozaki, Y., Watson, S.P., 2006. A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2. Blood 107, 542–549.

    Article  PubMed  CAS  Google Scholar 

  • Taniuchi, Y., Kawasaki, T., Fujimura, Y., Suzuki, M., Titani, K., Sakai, Y., Kaku, S., Hisamichi, N., Satoh, N., Takenaka, T., Handa, M., Sawai, Y., 1995. Flavocetin-A and -B, two high molecular mass glycoprotein Ib binding proteins with high affinity purified from Trimeresurus flavoviridis venom, inhibit platelet aggregation at high shear stress. Biochim. Biophys. Acta 1244, 331–338.

    Article  PubMed  Google Scholar 

  • Uhrin, P., Zaujec, J., Breuss, J.M., Olcaydu, D., Chrenek, P., Stockinger, H., Fuertbauer, E., Moser, M., Haiko, P., Fässler, R., Alitalo, K., Binder, B.R., Kerjaschki, D., 2010. Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulation. Blood 115, 3997–4005.

    Google Scholar 

  • Usami, Y., Fujimura, Y., Suzuki, M., Ozeki, Y., Nishio, K., Fukui, H., Titani, K., 1993. Primary structure of two-chain botrocetin, a von Willebrand factor modulator purified from the venom of Bothrops jararaca. Proc. Natl. Acad. Sci. U.S.A. 90, 928–932.

    Article  PubMed  CAS  Google Scholar 

  • Valentin, E., Lambeau, G., 2000. What can venom phospholipases A2 tell us about the functional diversity of mammalian secreted phospholipases A2? Biochimie 82, 815–831.

    Article  PubMed  CAS  Google Scholar 

  • Wang, R., Kong, C., Kolatkar, P., Chung, M.C., 2001. A novel dimer of a C-type lectin-like heterodimer from the venom of Calloselasma rhodostoma (Malayan pit viper). FEBS Lett. 508, 447–453.

    Article  PubMed  CAS  Google Scholar 

  • Wang, W.J., Huang, T.F., 2001. A novel tetrameric venom protein, agglucetin from Agkistrodon acutus, acts as a glycoprotein Ib agonist. Thromb. Haemost. 86, 1077–1086.

    PubMed  CAS  Google Scholar 

  • Wei, Q., Lu, Q.M., Jin, Y., Li, R., Wei, J.F., Wang, W.Y., Xiong, Y.L., 2002. Purification and cloning of a novel C-type lectin-like protein with platelet aggregation activity from Trimeresurus mucrosquamatus venom. Toxicon. 40, 1331–1338.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Haematology, University of Berne, Inselspital, CH-3010, Berne, Switzerland

    Kenneth J. Clemetson

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Correspondence to Kenneth J. Clemetson .

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Editors and Affiliations

  1. , Department of Biological Sciences, National University of Singapore, Science Drive 4 14, Singapore, 117543, Singapore

    R. Manjunatha Kini

  2. , Department of Haematology, University of Berne, Inselspital, Bern, CH-3010, Switzerland

    Kenneth J Clemetson

  3. , Biochemistry and Molecular Biology, University of Southern California, Health Sciences Campus/9270, Los Angeles, 90089, USA

    Francis S. Markland

  4. , Medical Technology, University of Delaware, 305G Willard Hall Educ Bld, Newark, 19716, Delaware, USA

    Mary Ann McLane

  5. , Biochemistry, Meiji Pharmaceutical University, Nishio Kiyose 2-522-1, Tokyo, 204-8588, Japan

    Takashi Morita

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Clemetson, K.J. (2010). Snaclecs (Snake C-Type Lectins) that Activate Platelets. In: Kini, R., Clemetson, K., Markland, F., McLane, M., Morita, T. (eds) Toxins and Hemostasis. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9295-3_35

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